An old - fashioned pure - blood wizard who doesn't like Hermione's Muggle - born status. He sees her as an outsider and wants to make her life difficult at Hogwarts. He uses a charm that causes water to seep through her clothes whenever she enters certain areas of the castle. This is his way of trying to drive her out of Hogwarts.
One possible plot could be that she's caught in a sudden rainstorm during a crucial moment, like when she's on a mission to find a hidden magical object. The rain soaks her, and she's frustrated because it might ruin the parchment with the clues she has. And she can't use a spell to dry off immediately as it might draw unwanted attention from dark forces in the area.
It could be an old and powerful vampire who sees Hermione as a threat to his rule. Since Hermione is a very intelligent witch - now vampire - she might be able to figure out a way to undermine his power.
It could be Ladybug. If Adrien turns villain, Ladybug would be the natural antagonist as she represents the good side. Their relationship would be completely flipped from what it was before. She would have to try to stop him from causing more harm, all while probably still having some feelings for the old Adrien.
Some dark wizards or witches who oppose the new order at Hogwarts after the fall of Voldemort could also be the villains. They might see Hermione as a threat to their plans of taking over or causing chaos in the wizarding world. They could force her to do things against her will in order to gain an advantage over the good side.
Gary could be the main antagonist. He has always been Ash's rival and seeing Ash turn evil, he might feel responsible to stop him. Gary could gather his own team of powerful Pokémon and use his wits to oppose Ash at every turn.
It could be that an external force, like a dark wizard in disguise, is the main antagonist. This dark wizard targets Hermione because of her potential to be a great threat to their evil plans. They use magic to cloud the minds of her friends, making them believe Hermione is up to no good. The friends, being under this spell, betray Hermione without realizing they are being manipulated. The dark wizard then watches as Hermione struggles with this betrayal, all part of their grand scheme.
It could be a jealous student who wants to undermine Hermione's intelligence. They might have cast the spell to turn her into a baby thinking it would be a great way to get her out of the way. This student could be someone who is always overshadowed by Hermione in class and exams.
Another possibility is an ancient evil that has been awakened. This entity might see Hermione as a threat because of her potential power. So it curses her to stop her from growing stronger. In this case, the antagonist would be very powerful and mysterious, and Hermione and her friends would have to do a lot of research and exploration to find a way to defeat it.
Hawk Moth would be an obvious choice as he is the main antagonist in the original series. He could create an akuma specifically designed to target Ladybug when she is in a wet or water - related situation. Maybe an akuma that can control water currents and use them to attack Ladybug, making her 'wet for me' part of the akuma's strategy to weaken or distract her.
It could be a powerful vampire who doesn't like Bella's new - found strength. This vampire might see her as a threat to their own power and control in the vampire world.